Aggressive T-cell large granular lymphocytic leukemia represents a rare but highly fatal clinical entity, starkly contrasting with the typically indolent nature of classic large granular lymphocytic leukemia. This report details the case of a female in her early 60s who succumbed to the disease merely 3 days after hospitalization, highlighting a precipitous clinical course from unremarkable blood test results to death within approximately 4 months. The diagnosis was confirmed by peripheral blood morphology, immunophenotyping, and molecular cytogenetic studies. The leukemic cells demonstrated a natural killer T-cell phenotype, clonal T-cell receptor rearrangement, and a complex karyotype. A significant outcome of this case was the successful establishment of a stable cell line derived from the patient's peripheral blood mononuclear cells. This case underscores the need for early recognition of this aggressive T-cell large granular lymphocytic leukemia variant. Furthermore, the novel cell line provides an invaluable and unprecedented resource for elucidating the underlying pathogenesis and exploring potential therapeutic strategies for this devastating malignancy.

BACKGROUND:Bufalin is one main component of the dried venom from Bufo gargarizans Cantor, which has anti-tumor, cardiotonic, anti-inflammatory and other physiological activities. However, in recent years, researchers have mainly paid attention to its anti-tumor effect and neglected its anti-inflammatory effect. METHODS:We used lipopolysaccharide (TLR4 ligand) and poly inosinic acid (TLR3 ligand) to stimulate cultured macrophages to induce inflammatory condition. Transcriptome sequencing and molecular experiments were performed to investigate the underlying mechanism. RESULTS:Bufalin could significantly reduce the production of pro-inflammatory factors (IL-6, TNF-α, IL-1β, IL-8, CXCL10, etc.), through inhibiting the phosphorylation of IKBα and IRF3, and thus down-regulating Toll-like receptor pathway. Molecular docking predicted that one of the molecular targets of bufalin is MD-2 coupled with lipopolysaccharide-activated TLR4. CONCLUSION:These findings not only support the pharmacological basis of using toad to treat inflammatory diseases in the Chinese medical history, but also provide a promising anti-inflammatory drug candidate for future clinical application.

Hemophagocytic lymphohistiocytosis (HLH) is a group of hyperinflammatory disorders with a mortality rate exceeding 50%. We report a case of a female Asian patient who developed secondary HLH accompanied by aggressive natural killer cell leukemia and Epstein-Barr virus (EBV) infection, and was treated with tripterygium glycosides (TG), a Chinese patent medicine. Within 3 weeks of oral administration, the patient's recurrent high fever resolved, abdominal distension and splenomegaly improved, ascites diminished, serum soluble CD25 levels decreased, and hematopoietic and coagulation functions recovered. Triptolide, a major component of TG, exhibited cytotoxicity against the patient's ascitic cells and induced apoptosis in a dose-dependent manner ex vivo. Whole-genome and transcriptome sequencing of the patient's tumor cells revealed that TG regulated EBV-associated mutated genes such as PSMD7 and modulated inflammation-related pathways. Molecular docking further suggested direct targeting of PSMD7 by triptolide. Tripterygium glycosides quickly mitigated cytokine storm, alleviated symptoms of HLH, and showed no observed adverse effects with a good cost-benefit profile, thereby offering a potential bridge for follow-up hematopoietic stem cell transplantation.

Cellular senescence is fundamentally characterized as an irreversible cell cycle arrest state.Studies have revealed that cellular senescence plays a significant role in the pathogenesis and progression of hematological malignancies.Consequently,inducing cellular senescence has emerged as a therapeutic strategy for these malignancies.Traditional Chinese herbal medicine,characterized by its high efficacy and relatively low toxicity,has shown unique potential in inducing senescence in hematological tumor cells.Previous studies have shown that traditional Chinese herbal medicine can induce cellular senescence through mechanisms such as telomere shortening,DNA damage induction,and regulation of the senescence-associated secretory phenotype(SASP)to treat hematological malignancies.This review aims to summarize the recent advances in the mechanisms by which cellular senescence contributes to the pathogenesis of hematological malignancies and the role of traditional Chinese herbal medicine in inducing cellular senescence for therapeutic purposes,thereby providing novel insights and theoretical support for the application of traditional Chinese herbal medicine in the treatment of hematological malignancies.

Introduction Hematological malignancies (HM) are heterogeneous with complex pathophysiology. Glycans, the third major informational biopolymer, surpass nucleic acids and proteins in structural complexity and information density. As a prevalent post-translational modification, glycosylation serves as a functional readout of genetic variants and drives HM development. However, HM glycomics research is at an early stage compared to other omics fields. Therefore, we conducted the largest multi-center clinical study to date in the field of HM glycomics, mapping the total blood N-glycome (TBNG) landscape across HM subtypes and treatment phases. Methods Patients were enrolled from a multi-center observational clinical study registered with the Chinese Clinical Trial Registry (ChiCTR) (Registration number: ChiCTR2400089864). Participants were recruited from 8 medical centers. TBNG features in HM were investigated using retrospective samples and prospective longitudinal samples. The study was approved by the Medical Ethics Committee of the Affiliated Drum Tower Hospital of Nanjing University Medical School (IRB No. 2024-654-01) and conducted in accordance with the Declaration of Helsinki. Serum N-glycan profiling was performed using capillary electrophoresis. Serum N-glycan detection followed previously described methods (Su R et al. Hepatology 2025). Nine specific serum N-glycan peaks were identified per sample. Results TBNG analysis was performed on 979 HM patients from 8 centers (April 2016 - April 2024), including 348 MM (35.5%), 370 lymphoma (37.8%), and 261 acute leukemia (AL) (26.7%) cases. The retrospective cohort included 923 patients (94.3%) (samples only at diagnosis or a single post-treatment follow-up point) while the prospective longitudinal cohort included 56 patients (5.7%) (samples at diagnosis and complete remission (CR) follow-up). Analysis covered 1,035 samples: 641 at diagnosis (ND), 59 at PR/VGPR, 257 at CR, and 78 at relapse/refractory (R/R). Healthy controls (n=150) were included. Firstly, we identified distinct TBNG profiles differentiated HM types. All HM patients (MM, lymphoma, AL) showed elevated triantennary glycan Peak9 (NA3Fb) vs. controls (p < 0.0001). TBNG also correlated with subtypes and risk stratification. In MM, IgG type showed increases in two monogalactosyl N-glycans (Peak3 and Peak4, NG1A2F; p < 0.0001), IgA type showed increase in biantennary glycan Peak7 (NA2FB, p < 0.0001), and light chain (LC) type showed increase in Peak9 (p < 0.0001). In DLBCL, elevated Peak9 correlated with aggressiveness and tumor burden: higher in aggressive vs. indolent lymphomas (p=0.022), Group B vs. A (p=0.0002), and stage III/IV vs. I/II (p=0.018). These findings support TBNG's potential as a biomarker for HM diagnosis, subtyping, and risk stratification. More importantly, we observed that the above-mentioned characteristic glycan changes vary with different disease remission statuses. Retrospective analysis confirmed significant differences in TBNG between ND and CR states. For IgG MM, Peak3 and Peak4 significantly decreased at CR compared to ND (p < 0.0001). For IgA MM, Peak7 decreased at CR (p < 0.0001). For LC MM, Peak9 decreased at CR (p = 0.0002). DLBCL and AML patients showed decreases in Peak9 at CR (p = 0.0006). TBNG profile at CR tends to be closer to that of healthy individuals, while the R/R group exhibited TBNG characteristics more similar to the ND group. To validate the findings from the retrospective study, we conducted an additional analysis focusing on the longitudinal changes in N-glycan patterns before and after treatment in 56 patients. The prospective cohort results confirmed retrospective TBNG trends between ND and CR states, supporting TBNG's potential as a biomarker for treatment response and MRD monitoring. Conclusion Using the largest HM blood cohort analyzed glycomically to date, this study delineates the comprehensive TBNG landscape in real-world patients. The findings suggest that different disease entities, subtypes, and stages of HM exhibit characteristic TBNG alterations. Furthermore, these TBNG signatures dynamically change in response to treatment and corresponding disease remission status. This TBNG landscape establishes its utility as a novel biomarker for HM diagnosis, subtyping, risk stratification, treatment response, and MRD monitoring.

Type B lactic acidosis (LA), a rare yet fatal complication of lymphoma with poor prognosis, remains poorly characterized due to reliance on isolated case reports. To systematically delineate clinical characteristics and prognostic determinants in newly diagnosed lymphoma patients presenting with LA as the initial presentation, we conducted an integrated analysis synthesizing unpublished institutional cases with systematically identified cases from PubMed, Web of Science, and hospital databases. Demographic, clinical, laboratory, imaging, histopathological, and therapeutic intervention data were extracted. Prognostic correlates were evaluated using univariate and multivariate logistic regression, with predictive accuracy validated through receiver operating characteristic (ROC) curves. Among the 53 patients analyzed, the predominant manifestations included general malaise and gastrointestinal symptoms (62.3

Natural killer T cells (NKT), a unique subset of T lymphocytes, remain incompletely understood in terms of their development and functional regulation. Well-characterized immortalized cell lines are critical tools for investigating NKT cell biology in vitro. We established and maintained a novel NKT cell line, NKT617, derived from the peripheral blood of a patient with aggressive large granular lymphocyte leukemia. Cell morphology was assessed using scanning electron microscopy and transmission electron microscopy. Flow cytometry characterized the cell phenotype, whereas T-cell receptor (TCR) clonal gene rearrangement determined lineage. RNA sequencing compared gene expression profiles of NKT617 with other hematological tumor cell lines, such as natural killer (NK) cells, T cells, B cells, and monocytes. Tumorigenic potential was evaluated via in vitro colony formation assays and in vivo zebrafish xenograft models. NKT617 has been continuously cultured for >2 years, exceeding 100 passages, demonstrating monoclonal immortalization. It proliferates in a low-dose recombinant human interleukin-2-dependent manner and grows in suspension culture as single cells and aggregates. Flow cytometric analysis showed that NKT617 exhibits an NK-cell phenotype CD56+, CD158a+, NKp46+, membrane-bound CD3-, and T-cell features cytoplasmic CD3+, CD2+, CD4+, CD8+, CD45RA+, and CD45RO+, with clonal TCRβ rearrangement. NKT617 was negative for B-cell and myeloid markers and positive for the TCRα chain (Vα24-Jα18), confirming its identity as a type I NKT cell. Transcriptome analysis showed shared markers with NK-cell and T-cell lines but a gene expression profile closer to NK cells. In vitro and in vivo assays confirmed its tumorigenic capacity. We report the first Epstein-Barr virus-negative human type I NKT cell line, NKT617, which offers significant potential for studying NKT cell development and advancing chimeric antigen receptor-based therapies. This cell line serves as a valuable tool for exploring NKT cell biology and developing targeted immunotherapies.

Purpose:Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent inflammation, pain, and joint destruction, largely driven by inflammation and oxidative stress. This study explored the therapeutic potential of a thermosensitive hydrogel (TPTH) loaded with TP-P1, a derivative of triptolide, focusing on anti-inflammatory and antioxidant effects. Methods:A collagen-induced arthritis (CIA) model was established by dual immunization with type II collagen and Freund's adjuvant. Mice were randomized into control, model, dexamethasone (DEX), blank hydrogel, and TPTH groups. After 28 days of intra-articular treatment, arthritis severity was assessed by paw swelling, arthritis scores, and histopathology. Cytokines (IL-6, IL-1β, TNF-α) were measured by RT-qPCR and flow cytometry, oxidative stress markers (MDA, SOD, CAT, GSH) were determined, and TLR4/NF-κB expression was analyzed by Western blotting, immunohistochemistry, and RT-qPCR. Biosafety was evaluated via liver/kidney histology and plasma indices (ALT, AST, BUN, CRE). Results:TPTH treatment markedly alleviated arthritis symptoms, reducing paw swelling and scores (p < 0.0001). It downregulated inflammatory cytokines, improved antioxidant status (SOD, CAT, GSH) and decreased MDA. TPTH also suppressed TLR4 and NF-κB expression, indicating modulation of inflammatory signaling. Importantly, no obvious hepatic or renal toxicity was observed. Conclusion:TPTH significantly ameliorates inflammation and oxidative stress in CIA mice by modulating the TLR4/NF-κB pathway and shows promise as a safe and effective therapeutic strategy for RA.

ETHNOPHARMACOLOGICAL RELEVANCE:Multiple myeloma (MM) is a common hematologic malignancy. Huachansu (HCS) is extracted from the skin of Bufo bufo gargarizans, known for its well-established and multi-target anti-tumor effect. It has been reported to be effective in treating patients with multiple myeloma but its underlying mechanism remains unclear. AIM OF THE STUDY:This study aims to investigate the cellular and molecular mechanisms in which HCS induces cell death of MM. MATERIALS AND METHODS:Cell viability was assessed using the CCK-8 assay. The effect of HCS on the gene expression of MM were screened by transcriptome sequencing and validated by quantitative real-time PCR, Western blot, and immunofluorescence. The ferroptosis phenotype were evaluated by measuring iron ion concentration, lipid peroxidation degree in terms of malondialdehyde (MDA), and reduced glutathione (GSH) level. Flow cytometry was adopted to measure intracellular ROS and PGSK levels. The ability of ferroptosis inhibitors to reverse these effects was also assessed. The treatment effect and ferroptosis induction of HCS on MM in vivo were explored on a xenograft nude mice model, with mitochondrial damage observed by transmission electron microscopy. RESULTS:HCS modulated the NRF2/HO-1 pathway, upregulating PRP and ZIP8, leading to Fe2+ accumulation and PGSK elevation, while increasing ROS and MDA levels and reducing GSH content. These effects were significantly reversed by the ferroptosis inhibitor Ferrostin-1. HCS induced MM cell ferroptosis through the NRF2/HO-1 pathway in vivo, inhibiting MM progression similarly to the positive control drug bortezomib. CONCLUSION:These results indicate that HCS can induce ferroptosis in MM cells via the NRF2/HO-1 pathway, thereby controlling MM progression. Our study provides a solid theoretical basis for the clinical use of HCS in treating MM. Additionally, it suggests an innovative treatment alternative based on natural medicine, proposing the combined use of HCS and chemotherapy drugs as a new therapeutic avenue for MM.

Rationale: Cytokine storm is now considered to be a systemic inflammatory response, but local cytokine storm may exist in systemic diseases of the blood system. Monitoring of regional cytokine storm is an important clue for the diagnosis of systemic diseases. Patient concerns: A 72-years-old male presented to our hospital with multiple serosal effusion without solid mass or enlarged lymph nodes. We found that the level of cytokines in ascites was tens to hundreds of times higher than that in plasma, mainly IL-6 and IL-8. Diagnoses: The patient was diagnosed with multiple serous effusion, hemophagocytic syndrome, B-cell lymphoma, Epstein–Barr virus infection, and hypoproteinemia. Interventions: During hospitalization, the patient was treated with 5 courses of R-CVEP therapy and supportive treatment. Outcomes: After the first R-CVEP regimen, the patient’s condition was evaluated as follows: hemophagocytic syndrome improved: no fever; Serum triglyceride 2.36 mmol/L; Ferritin 70.70 ng/L; no hemophagocyte was found in the bone marrow; the lymphoma was relieved, ascites disappeared, and bone marrow cytology showed: the bone marrow hyperplasia was reduced, and small platelet clusters were easily seen. Bone marrow flow cytometry showed that lymphocytes accounted for 13.7%, T cells increased for 85.7%, CD4/CD8 = 0.63, B cells decreased significantly for 0.27%, and NK cells accounted for 10.2%. Blood routine returned to normal: WBC 5.27 × 109/L, HB 128 g/L, PLT 129 × 109/L; Epstein–Barr virus DNA < 5.2E + 02 copies/mL; correction of hypoproteinemia: albumin 39.7 g/L. Lessons: Cytokines in ascites are significantly higher than those in plasma by tens to hundreds of times, suggesting that “regional cytokine storms” may cause serosal effusion.

OBJECTIVE:The leukemia cells from patients with T-cell acute lymphoblastic leukemia (T-ALL) were inoculated into NCG mice to establish a stable human T-ALL leukemia animal model.METHODS:Leukemia cells from bone marrow of newly diagnosed T-ALL patients were isolated, and the leukemia cells were inoculated into NCG mice via tail vein. The proportion of hCD45 positive cells in peripheral blood of the mice was detected regularly by flow cytometry, and the infiltration of leukemia cells in bone marrow, liver, spleen and other organs of the mice was detected by pathology and immunohistochemistry. After the first generation mice model was successfully established, the spleen cells from the first generation mice were inoculated into the second generation mice, and after the second generation mice model was successfully established, the spleen cells from the second generation mice were further inoculated into the third generation mice, and the growth of leukemia cells in peripheral blood of the mice in each group was monitored by regular flow cytometry to evaluate the stability of this T-ALL leukemia animal model.RESULTS:On the 10th day after inoculation, hCD45+ leukemia cells could be successfully detected in the peripheral blood of the first generation mice, and the proportion of these cells was gradually increased. On average, the mice appeared listless 6 or 7 weeks after inoculation, and a large number of T lymphocyte leukemia cells were found in the peripheral blood and bone marrow smear of the mice. The spleen of the mice was obviously enlarged, and immunohistochemical examination showed that hCD3+ leukemia cells infiltrated into bone marrow, liver and spleen extensively. The second and third generation mice could stably develop leukemia, and the average survival time was 4-5 weeks.CONCLUSION:Inoculating leukemia cells from bone marrow of patients with T-ALL into NCG mice via tail vein can successfully construct a patient-derived tumor xenografts (PDTX) model.

目的:通过构建表达IL-12的小鼠CAR-T细胞,探讨经尾静脉将其输注于小鼠体内建立细胞因子释放综合征(CRS)模型的方法.方法:构建基于靶向鼠源CD19的CAR分子,包装逆转录病毒载体并感染小鼠T细胞构建mCD19-CAR-T、mCD19/IL-12-CAR-T细胞.通过构建小鼠体内胰腺癌Panc02-CD19细胞移植瘤模型,检测mCD19/IL-12-CAR-T细胞的抗肿瘤活性,ELISA法检测两种CAR-T细胞IL-12和IFN-γ分泌水平;经小鼠尾静脉输注mCD19/IL-12-CAR-T细胞构建CAR-T细胞CRS小鼠模型,流式细胞术检测小鼠血清中IL-6、MCP-1、IL-1、IL-10、TNF-α、IFN-γ等细胞因子的含量,H-E染色法观察荷瘤小鼠肝、脾、肺和肾的病理组织学变化.结果:经过培养扩增的mCD19/IL-12-CAR-T细胞能有效分泌IL-12,CAR阳性率达(56.9±5.4)％;与非靶细胞Panc02或靶细胞Panc02-CD19共培养时,均能高分泌IFN-γ.成功构建小鼠胰腺癌Panc02-CD19细胞移植瘤模型,经小鼠尾静脉注射1×106个mCD19/IL-12-CAR-T细胞能显著抑制移植瘤的生长,但未能诱发严重CRS;输注2×106个mCD19/IL-12-CAR-T细胞后,小鼠出现体质量减轻、血清炎性因子水平升高、组织损伤,最终导致死亡等一系列典型CRS表现.结论:成功构建IL-12-CAR-T细胞诱发的小鼠CRS模型,其稳定性好、重复性高,具有广泛的应用前景.

OBJECTIVE:To investigate the inflammatory effects of Cinobufotalin on monocytes in resting state and macrophages in activated state and its molecular mechanism.METHODS:THP-1 cells were stimulated with Phorbol 12-myristate 13-acetate to induce differentiation into macrophages. Lipopolysaccharides was added to activate macrophages in order to establish macrophage activation model. Cinobufotalin was added to the inflammatory cell model for 24 h as a treatment. CCK-8 was used to detect cell proliferation, Annexin V /PI double staining flow cytometry was used to detect cell apoptosis, flow cytometry was used to detect macrophage activation, and cytometric bead array was used to detect cytokines. Transcriptome sequencing was used to explore the gene expression profile regulated by Cinobufotalin. Changes in the significantly regulated molecules were verified by real-time quantitative polymerase chain reaction and Western blot.RESULTS:1∶25 concentration of Cinobufotalin significantly inhibited the proliferation of resting monocytes(P<0.01), and induced apoptosis(P<0.01), especially the activated macrophages(P<0.001, P<0.001). Cinobufotalin significantly inhibited the activation of macrophages, and significantly down-regulated the inflammatory cytokines(IL-6, TNF-α, IL-1β, IL-8) released by activated macrophages(P＜0.001). Its mechanism was achieved by inhibiting TLR4/MYD88/P-IκBa signaling pathway.CONCLUSION:Cinobufotalin can inhibit the inflammatory factors produced by the over-activation of macrophages through TLR4/MYD88/P-IκBa pathway, which is expected to be applied to the treatment and research of diseases related to the over-release of inflammatory factors.

单细胞测序技术正逐渐成为生物学基础研究的"必备工具",为我们理解各种生物学现象带来革命性的洞见.很多传染性疾病均涉及免疫细胞的差异化功能,而这些免疫细胞之间具有较大的异质性.与传统的批量高通量测序相比,近年来新兴的单细胞转录组测序使得研究者能够分析感染过程的免疫细胞异质性,充分挖掘珍贵的临床样本的分子信息,还能获取难以培养的病原微生物的遗传信息.本文着重介绍了当前单细胞测序在传染性疾病及病原微生物研究领域中的应用情况,并对其发展前景做了简要展望.

再生障碍性贫血是临床上常见的慢性、难治性血液疾病之一,其发病机制目前尚未完全阐明.现阶段中医与西医治疗此病均有各自的优势和不足.为了进一步提高此病患者的疗效,临床上常对其进行中西医结合治疗.本文主要对再生障碍性贫血的中西医发病机制及治疗进展进行简要综述,并总结了用养血平障汤治疗再生障碍性贫血的疗效及作用机理,以期为中西医结合治疗本病提供依据.

OBJECTIVE To investigate the short-term and long-term curative efficacy of low-intensity traditional chemotherapy regimen for elderly patients with acute myeloid leukemia (AML, non-M3) and related adverse reactions, in order to explore whether low-intensity traditional chemotherapy regimen still has application value in the treatment of elderly AML patients today. METHODS The clinical characteristics, treatment response and prognosis of 67 elderly patients with AML (non-M3) admitted to our hospital from June 2008 to December 2018 were retrospectively analyzed. All patients received low-intensity conventional chemotherapy (i.e. lower standard dose, and without new drugs listed in China since the 21st century), including DA, HA, CAG, etc. The CR rate, median survival time and 5-year cumulative survival rate of patients were evaluated, and the related indexes were compared with the data reported in domestic and foreign literatures at the same time. RESULTS The CR rate was 55.2% (37/67), the median survival time was 13.7 months, and the 5-year cumulative survival rate was (24.4±6.3)% in patients received low-intensity tradional chemotherapeutic regimens. The CR rates of high-risk group and non-high-risk group were 38.7% (12/31) and 69.4% (25/36), respectively; the median survival time of high-risk group and non-high-risk group was 8.9 months and 25.2 months respectively; the 5-year cumulative survival rate of high-risk group was (10.2±6.6)% and that of non-high-risk group was (36.0± 9.4)%. Compared with the data reported in the literature at the same time, the data obtained from the low-intensity traditional chemotherapy regimen for the elderly AML did not have an obvious disadvantage, morever had relatively short bone marrow suppression time, low induction early mortality rate and low incidence of severe infection. CONCLUSION At present, the low-intensity traditional chemotherapy regimen still has good curative effect and survival advantages for elderly AML patients, especially for non-high-risk patients. The adverse reactions are controllable, and the physical and economic conditions of the vast majority of patients can bear the treatment regimen.

蟾毒灵(Bufalin)为我国传统中药蟾酥的主要抗肿瘤活性成分,具有解毒、镇痛、开窍、强心以及抗肿瘤等功效.近几年深入研究指出蟾毒灵能够影响多种恶性肿瘤的发生发展,如肝癌、肺癌、胰腺癌、胃癌、结肠癌及卵巢癌等.蟾毒灵展现出了传统中药抗肿瘤的独特优势与抗肿瘤活性,有望实现传统中药抗肿瘤的新突破.主要从蟾毒灵的发展历史、主要作用靶点、主要作用的信号通路及蟾毒灵结构修饰四大部分对近几年蟾毒灵药物的研究进展进行综述,并且总结了蟾毒灵存在的问题与挑战.

目的:遵仲景“辨病审证”之思维及“同中见异,异中求同”之法,归纳总结相关经方,以期为恶性血液病化疗提供理论与用药指导.方法:通过对《伤寒杂病论》中的条文进行归纳总结,探析其病因病机与治法方药,并与恶性血液病化疗所致毒副反应的病因病机相联系,探索治疗新思路.结果:恶性血液病化疗过程中出现各种毒副反应,均可根据病因病机之不同,选取合适的经方治疗.结论:仲景方在恶性血液病化疗中具有重要的指导价值.

The novel coronavirus (SARS-CoV-2/ 2019-nCoV) identified in December 2019 has caused great damage to public health and economy worldwide. Previous research has suggested an involvement of meteorological conditions in the spread of droplet-mediated viral diseases, such as influenza. However, as for the recent novel coronavirus, few studies have discussed systematically about the role of daily weather in the epidemic transmission of the virus. Here, we examine the relationships of meteorological variables with the severity of the outbreak on a worldwide scale. The confirmed case counts, which indicates the severity of COVID-19 spread, and four meteorological variables, i.e., air temperature, relative humidity, wind speed, and visibility, were collected daily between January 20 and March 11 (52 days) for 430 cities and districts all over China, 21 cities/ provinces in Italy, 21 cities/ provinces in Japan, and 51 other countries around the world. Four different time delays of weather (on the day, 3 days ago, 7 days ago, and 14 days ago) as to the epidemic situation were taken formodeling and we finally chose the weather two weeks ago to model against the daily epidemic situation as its correlated with the outbreak best. Taken Chinese cities as a discovery dataset, it was suggested that temperature, wind speed, and relative humidity combined together could best predict the epidemic situation. The meteorological model could well predict the outbreak around the world with a high correlation ( r 2 > 0.6) with the real data. Using this model, we further predicted the possible epidemic situation in the future days for several high-latitude cities with potential outbreak. This model could provide more information for government’s future decisions on COVID-19 outbreak control. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work is supported by the Priority Academic Program Development of Jiangsu Higher Education Institutions-the third period (035062002003c) and the Yizhong Research Promoting Grand of the Jiangsu Province Hospital of Chinese Medicine (Y19066). ### Author Declarations All relevant ethical guidelines have been followed; any necessary IRB and/or ethics committee approvals have been obtained and details of the IRB/oversight body are included in the manuscript. Yes All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Data are available upon request by email.

Prognosis of patients with Philadelphia-positive acute lymphoblastic leukemia (Ph-ALL) relapsing after allogeneic hematopoietic stem cell transplantation (HSCT) is extremely poor. Therefore, effective alternative therapeutic measures are urgently needed. Recently, the use of antigen receptor-modified T cells holds great promise for relapsed and refractory ALL treatment. Prior to chimeric antigen receptor T-cell (CAR-T) infusion conditioning chemotherapy is used routinely to establish a favorable in vivo environment for CAR-T expansion, which has mostly involved fludarabine and cyclophosphamide. We report on a patient presented with extreme fatigue and anemia and was diagnosed with relapsed and refractory acute lymphoblastic leukemia (ALL) harbored T315I-BCR-ABL mutation, who had undergone allogeneic HSCT and multiple reinducing chemotherapy, but achieved complete hematologic remission (CHR) with CAR -T infusion as a later salvage treatment. Prior to CAR-T infusion there was no conditioning chemotherapy, but a bone marrow suppression period induced by ponatinib. CAR-T cell infusion was well tolerated and the patient achieved a CHR and maintained it for three months. At present, there is no relevant report on the use of tyrosine kinase inhibitors (TKI) as preconditioning protocols before CAR-T cells infusion. Our case indicated ponatinib not only reduces tumor burden but may also serve as a conditioning regimen for CAR-T therapy in the treatment of relapsed and refractory Ph-ALL.